{"created":"2023-05-15T14:56:31.609999+00:00","id":76736,"links":{},"metadata":{"_buckets":{"deposit":"faddca9f-ce32-423b-868f-7a8c6c824eab"},"_deposit":{"created_by":1,"id":"76736","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"76736"},"status":"published"},"_oai":{"id":"oai:repo.qst.go.jp:00076736","sets":["10:28"]},"author_link":["782801","782813","782806","782817","782795","782815","782800","782799","782796","782808","782807","782818","782805","782803","782810","782814","782804","782811","782812","782802","782798","782816","782797","782809"],"item_10005_date_7":{"attribute_name":"発表年月日","attribute_value_mlt":[{"subitem_date_issued_datetime":"2019-09-07","subitem_date_issued_type":"Issued"}]},"item_10005_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background and Objectives: Designing small-molecule radiopharmaceuticals targeting an oncoprotein, such as the ectopic metabotropic glutamate receptor 1 (mGluR1) in melanoma [1], is an attractive strategy to increases our ability to deliver therapeutics to tumor tissues with high precision in targeted radionuclide therapy (TRT). Herein, we focused on 4-fluoro-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-methylbenzamide (FITM), a small-molecule compound with high affinity and specificity for the oncoprotein mGluR1[2,3], as the target carrier, with an -emitter (211At) to design and synthesize a novel TRT radiopharmaceutical: 4-211At-astato-N-[4-(6-(isopropylamino)pyridine-4-yl)-1,3-thiazol-2-yl]-N-methylbenzamide (211At-AITM), and investigated its therapeutic efficacy and safety in mGluR1-expressing B16F10 melanomas. \nMethods: Radiosynthesis of 211At-AITM was carried out by reacting the stannyl precursor with 211At (Fig. 1A). The binding specificity of 211At-AITM to mGluR1-expressing melanoma cells was assessed with and without the parent compound containing no radionuclide, FITM. Therapeutic effect and safety assessment were performed with a single injection of 211At-AITM with conservative doses (0–2.96 MBq) to B16F10-bearing C57BL/6J mice.\nResults: 211At-AITM were stably obtained with radiochemical purity >99% and radiochemical yields of 28.9 ± 9.9% (n = 20), based on the radioactivity of the cyclotron-produced 211At. The radiopharmaceuticals 211At-AITM bound to B16F10 cells with 12.87 %ICD/mg, and were specifically displaced by the non-radiolabeled FITM. TRT with 211At-AITM markedly inhibited melanoma growth compared to the 0 MBq (saline) treated controls. Dose-dependent tumor inhibition was observed in melanoma mice treated with 0.11, 1.11, 1.85 or 2.96 MBq 211At-AITM. A single 0.11 MBq dose of  211At-AITM resulted in approximately 32.24% tumor reduction, but this was not statistically significant; other reductions based on the concentration administered include 73.48% at 1.11 MBq; 87.38% at 1.85 MBq; 95.68% at 2.96 MBq compared to the 0 MBq group at 19 days post-administration (Fig. 1B). Throughout the examination period, no weight loss, hepatotoxicity or nephrotoxicity were observed in melanoma mice injected with 0–2.96 MBq 211At-AITM (Fig. 1C).\nConclusions: Our results demonstrated the 211At labeled small-molecule radiopharmaceutical 211At-AITM possess high therapeutic efficiency and minimal health risks, thus could be attractive for clinical development as high-precision TRT weapons directed at the oncoprotein mGluR1 for melanoma therapy.\nReferences:\n1.Pollock PM, Cohen-Solal K, Sood R, et al. Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Nat Genet. 2003; 34:108-112.\n2.Xie L, Yui J, Fujinaga M, et al. Molecular imaging of ectopic metabotropic glutamate 1 receptor in melanoma with a positron emission tomography radioprobe 18 F-FITM. Int J Cancer. 2014;135:1852-9.\n3.Fujinaga M1, Xie L, Yamasaki T, et al. Synthesis and evaluation of 4-halogeno-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-[11C]methylbenzamide for imaging of metabotropic glutamate 1 receptor in melanoma. J Med Chem. 2015;58:1513-23.\n\n","subitem_description_type":"Abstract"}]},"item_10005_description_6":{"attribute_name":"会議概要（会議名, 開催地, 会期, 主催者等）","attribute_value_mlt":[{"subitem_description":"WMIC2019でのポスター発表","subitem_description_type":"Other"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"metadata only access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_14cb"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Xie, Lin"}],"nameIdentifiers":[{"nameIdentifier":"782795","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hanyu, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"782796","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujinaga, Masayuki"}],"nameIdentifiers":[{"nameIdentifier":"782797","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding"}],"nameIdentifiers":[{"nameIdentifier":"782798","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kuan, Hu"}],"nameIdentifiers":[{"nameIdentifier":"782799","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Minegishi, Katsuyuki"}],"nameIdentifiers":[{"nameIdentifier":"782800","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Jiang, Cuiping"}],"nameIdentifiers":[{"nameIdentifier":"782801","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kurosawa, Fuki"}],"nameIdentifiers":[{"nameIdentifier":"782802","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Morokoshi, Yukie"}],"nameIdentifiers":[{"nameIdentifier":"782803","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Li, Huizi"}],"nameIdentifiers":[{"nameIdentifier":"782804","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hasegawa, Sumitaka"}],"nameIdentifiers":[{"nameIdentifier":"782805","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nagatsu, Kotaro"}],"nameIdentifiers":[{"nameIdentifier":"782806","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ming-Rong, Zhang"}],"nameIdentifiers":[{"nameIdentifier":"782807","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Xie, Lin","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782808","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Hanyu, Masayuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782809","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Fujinaga, Masayuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782810","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Zhang, Yiding","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782811","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kuan, Hu","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782812","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Minegishi, Katsuyuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782813","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Kurosawa, Fuki","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782814","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Morokoshi, Yukie","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782815","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Li, Huizi","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782816","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Nagatsu, Kotaro","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782817","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"Ming-Rong, Zhang","creatorNameLang":"en"}],"nameIdentifiers":[{"nameIdentifier":"782818","nameIdentifierScheme":"WEKO"}]}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"conference object","resourceuri":"http://purl.org/coar/resource_type/c_c94f"}]},"item_title":"Effective therapy against melanoma using 211At labeled small-molecule radiopharmaceutical 211At-AITM by targeting oncoprotein metabotropic glutamate receptor 1  ","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Effective therapy against melanoma using 211At labeled small-molecule radiopharmaceutical 211At-AITM by targeting oncoprotein metabotropic glutamate receptor 1  "}]},"item_type_id":"10005","owner":"1","path":["28"],"pubdate":{"attribute_name":"公開日","attribute_value":"2019-09-06"},"publish_date":"2019-09-06","publish_status":"0","recid":"76736","relation_version_is_last":true,"title":["Effective therapy against melanoma using 211At labeled small-molecule radiopharmaceutical 211At-AITM by targeting oncoprotein metabotropic glutamate receptor 1  "],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2023-05-16T00:13:41.654812+00:00"}